Back to Search
Start Over
FFA-Fetuin-A regulates DPP-IV expression in pancreatic beta cells through TLR4-NFkB pathway.
- Source :
-
Biochemical & Biophysical Research Communications . Mar2023, Vol. 647, p55-61. 7p. - Publication Year :
- 2023
-
Abstract
- Dipeptidyl peptidase 4 (DPP-IV) is a ubiquitous proteolytic enzyme that cleaves incretin hormones, such as glucagon-like peptide 1 (GLP1) and gastric inhibitory protein (GIP), leading to reduced glucose stimulated insulin secretion from the pancreatic beta cells. The functionally active enzyme is present in a membrane bound form in several cell types as well as in a soluble form in the circulation. The present report deals with DPP-IV expression and its regulation in the pancreatic beta cells in presence of free fatty acids (FFAs) and Fetuin-A, a circulatory glycoprotein associated with insulin resistance in humans and animals. FFA and Fetuin-A individually or in combination trigger DPP-IV expression in MIN6 cells. Islets isolated from high fat diet fed (HFD) mice (16 weeks) showed higher levels of DPP-IV expression than standard diet (SD) fed mice. Fetuin-A increased DPP-IV expression in HFD mice (4 weeks). Inhibition of TLR4 or NFkB prevented palmitate-Fetuin-A mediated DPP-IV expression in MIN6. It has been seen that Fetuin-A alone also could trigger DPP-IV expression in MIN6 cells via NFkB. Additionally, palmitate treatment exhibited reduced level of soluble DPP-IV in the media of MIN6 culture, which corroborated with the expression pattern of its protease, KLK5 that cleaves and releases the membrane bound DPP-IV into the secretion. Our results demonstrate that FFA-Fetuin-A upregulates DPP-IV expression in the pancreatic beta cells through the TLR4-NFkB pathway. • FFA-Fetuin-A induces DPP-IV expression in the pancreatic beta cells. • Fetuin-A-palmitate mediated DPP-IV expression occurs through the activation of the TLR4-NFkB pathway. • Palmitate reduces the cleavage of membrane bound DPP-IV in MIN6 via KLK5 protease. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0006291X
- Volume :
- 647
- Database :
- Academic Search Index
- Journal :
- Biochemical & Biophysical Research Communications
- Publication Type :
- Academic Journal
- Accession number :
- 161719582
- Full Text :
- https://doi.org/10.1016/j.bbrc.2023.01.070